PB2646: THE COMPOSITE OF CHITOSAN WITH ASPARTIC ACID AS A PROMISING HEMOSTATIC AGENT
Authors: Tamara Obergan, Marina Grigorjeva, Tatiana Shubina, Ludmila Lyapina
Journal: HemaSphere (2023)

Topic: 33. Bleeding disorders (congenital and acquired) Background: Hemorrhagic conditions of various genesis can lead to hemocoagulation complications due to impaired reactions of vascular-platelet and plasma hemostasis. This is a serious problem of physiology and medicine, because in such cases massive bleeding can occur, which threatens the lives of patients. Currently, various highly active hemostatic agents are widely used for the relief of hemorrhages. In this regard, it is of interest to study chitosan-based biopolymers that exhibit a wide range of biological activities, including hemostatic, while having good biocompatibility and non-toxicity. However, the effect of chitosan and its composites on the blood clotting system remains unclear. Aims: To study the effect of a chitosan composite with aspartic acid on vascular-platelet hemostasis in animals with experimental hypocoagulation. Methods: The study was performed on male Wistar rats in accordance with the “International Guiding Principles for Biomedical Involving Animals”. 4 groups of animals were used: rats treated with composite of chitosan (100 mg/kg) with aspartic acid (2 mg/kg); rats treated rats treated with either chitosan or aspartic acid in doses equivalent to their content in the composite; rats treated with saline solution (as a control). All drugs were administered orally to rats daily once a day for 14 days. After the application of the studied drugs, the animals of each group orally received acetylsalicylic acid (aspirin) at a dose of 1.5 mg/kg to simulate experimental hypocoagulation, since aspirin is the most widely used antiplatelet drug with a clinically proven mechanism of action. Additionally, a group of intact rats was used. Blood samples from each animal were obtained 20 hours after completion of the course of treatment, and then ADP-induced platelet aggregation (according to Born) was evaluated in platelet-rich blood plasma of rats (final concentration of ADP 10-6 M). Results: During the experiment, it was shown that in animals injected with aspirin, a decrease in platelet aggregation was revealed by 30% (p < 0.05) in relation to intact rats, which indicated an increase in the antiplatelet potential of the blood and the development of a hypocoagulation state. Treatment of animal composite of chitosan with aspartic acid contributed to an increase in the hemostatic potential of the blood, which was expressed in an increase in platelet aggregation by 58% (p < 0.05) versus control. In animals treated with either chitosan or aspartic acid, platelet aggregation increased by 22% and 36% (p < 0.05 in both cases), respectively, versus the control group. Consequently, the composite showed a greater effect on primary hemostasis compared to its constituent parts – chitosan and aspartic acid, significantly enhancing platelet aggregation. Summary/Conclusion: Thus, the chitosan-based composite exhibits a noticeable procoagulant effect, restoring the hemostatic balance reduced as a result of aspirin use. Activation of the vascular-platelet link of hemostasis, due to increased platelet aggregation processes, may be a potential mechanism by which the composite of chitosan with aspartic acid normalizes hemostatic reactions under hypocoagulation conditions in the experiment. Based on this, the composite of chitosan with aspartic acid can be considered a promising hemostatic agent. Keywords: Bleeding disorder, Aspirin, Platelet aggregation, Procoagulant